Table of contents · 10 sections
In a nutshell. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS. Typical onset is at 20–40 years of age, F:M = 2–3:1. Diagnosis is based on the 2017 McDonald criteria (dissemination in space and time). Management: acute relapses are treated with methylprednisolone pulses; long-term management utilizes disease-modifying therapy (DMT).
1. Epidemiology and Risk Factors
The prevalence of MS in Russia is 30–70 per 100,000, showing a "northern gradient" (higher prevalence at higher latitudes). The most likely mechanism involves a combination of genetic susceptibility (HLA-DRB1*15:01) and environmental factors: Epstein-Barr virus, low vitamin D levels, smoking, and adolescent obesity.
2. Pathogenesis
Activated CD4⁺ T-helper cells (Th1, Th17) cross the blood-brain barrier and recognize myelin antigens (MBP, MOG, PLP) as foreign → activation of microglia and macrophages → demyelination and axonal damage. In later stages, a neurodegenerative component dominates with progressive brain and spinal cord atrophy.
3. Clinical forms
- Relapsing-remitting MS (RRMS) — 85% of disease onsets: clear-cut relapses with complete or incomplete recovery.
- Secondary progressive MS (SPMS) — develops after 10–20 years of RRMS; accumulation of disability without distinct relapses.
- Primary progressive MS (PPMS) — 10–15%: progression from onset, more common in men over 40, spinal cord involvement is typical.
- Clinically isolated syndrome (CIS) — the first episode of demyelination, does not yet meet criteria for MS.
- Radiologically isolated syndrome (RIS) — asymptomatic MRI lesions found incidentally.
4. Clinical presentation
Symptoms depend on the location of the lesions. Typical manifestations:
- Optic neuritis — decreased vision, pain with eye movement, Uhthoff's phenomenon (worsening with heat).
- Brainstem involvement: internuclear ophthalmoplegia, bilateral nystagmus, diplopia.
- Spinal cord syndrome: paresis, spasticity, sensory disturbances, bowel/bladder dysfunction, Lhermitte's sign (electric shock sensation down the spine upon neck flexion).
- Cerebellar signs: ataxia, intention tremor, nystagmus — Charcot's neurological triad.
- Cognitive impairment: reduced information processing speed, short-term memory deficits.
- Chronic fatigue — one of the most disabling symptoms.
5. Diagnostics: 2017 McDonald criteria
It is necessary to demonstrate dissemination in space (DIS) and dissemination in time (DIT) of lesions.
| Clinical Practice | Additional requirements |
|---|---|
| ≥ 2 attacks + objective evidence of ≥ 2 lesions | None — MS diagnosis |
| ≥ 2 attacks + ≥ 1 objective lesion | DIS on MRI or a new attack in a different region |
| 1 attack + ≥ 2 lesions | DIT on MRI (simultaneous contrast-enhancing and non-enhancing lesions) or CSF (oligoclonal bands) or by a follow-up MRI |
| 1 attack + 1 lesion (CIS) | DIS + DIT on MRI / CSF |
| PPMS | Progression for ≥ 1 year + 2 of 3: ≥ 1 T2 lesion in periventricular/juxtacortical/infratentorial regions; ≥ 2 T2 lesions in the spinal cord; CSF oligoclonal bands |
Typical MRI findings
- T2/FLAIR lesions in the periventricular zone ("Dawson's fingers" — perpendicular to the corpus callosum).
- Juxtacortical and infratentorial lesions.
- Spinal cord lesions.
- Active lesions enhance with contrast (gadolinium).
Cerebrospinal fluid
- Oligoclonal bands (IgG class) in CSF but not in serum — sensitivity > 95%.
- Elevated IgG index.
6. Differential diagnosis
- Neuromyelitis optica spectrum disorder (NMOSD) — aquaporin-4 antibodies.
- MOG antibody-associated disease (MOGAD).
- Neurosarcoidosis, neuroborreliosis, neurosyphilis.
- Systemic autoimmune diseases (SLE, APS, Sjögren's syndrome).
- Infarctions, CNS vasculitis.
- Leukodystrophies.
7. Relapse management
- Methylprednisolone 1 g IV drip for 3–5 days (pulse therapy). The goal is faster functional recovery; it does not alter the long-term prognosis.
- If steroids are ineffective — plasma exchange (5 sessions).
- For moderate relapses, an oral methylprednisolone regimen is an option.
8. Disease-modifying therapy (DMT)
The goal is to reduce relapse frequency and slow progression. Selection depends on disease activity, tolerability, and pregnancy planning.
| Group | Examples | Mechanism |
|---|---|---|
| Interferons beta | IFN-β 1a (Avonex, Rebif), IFN-β 1b (Betaferon) | Immunomodulation, ↓ crossing of the blood-brain barrier |
| Glatiramer acetate | Copaxone | "Decoy" for myelin antigens |
| Teriflunomide | Aubagio | Pyrimidine synthesis block in lymphocytes |
| Dimethyl fumarate | Tecfidera | Nrf2 activation — antioxidant, immunomodulation |
| Fingolimod, siponimod, ozanimod | — | S1P receptor agonists, "trap" lymphocytes in lymph nodes |
| Cladribine | Mavenclad | Selective depletion of B and T lymphocytes |
| Natalizumab | Tysabri | α4-integrin blockade — prevents lymphocytes from entering the brain |
| Anti-CD20 (ocrelizumab, ofatumumab) | Ocrevus, Kesimpta | B-lymphocyte depletion; the only ones approved for PPMS |
Strategies: stepwise (escalation) — start with moderate, switch upon progression; induction ("hit early, hit hard") — highly effective drug immediately for active forms.
9. Symptomatic therapy
- Spasticity — baclofen, tizanidine, gabapentin; botulinum toxin.
- Neuropathic pain — gabapentin, pregabalin.
- Fatigue — amantadine, modafinil.
- Depression — SSRIs.
- Bladder and bowel dysfunction — anticholinergics (oxybutynin), self-catheterization.
- Rehabilitation: exercise therapy, physical therapy, neuropsychological correction.
10. FAQ
Can MS be "benign"?
The term is conventional; in 10–20% of patients after 10 years, EDSS is ≤ 3.0. Modern doctrine is to start DMT even in "mild" cases to avoid hidden neurodegenerative progression.
Can one get pregnant with MS?
Yes. During pregnancy, the attack rate decreases; in the first 3 months postpartum, it increases. Most DMTs are stopped 1–3 months before conception; interferons and glatiramer are considered relatively safe.
How to distinguish MS optic neuritis from ischemic neuropathy?
MS ON — young age, subacute onset with pain, improvement within weeks; ischemic neuropathy — sudden painless vision loss in the elderly.
Does vitamin D help?
Maintaining a 25(OH)D level of 75–100 nmol/L is associated with a reduction in relapses and progression according to observational studies. 2000–4000 IU/day is recommended.
What is a "pseudo-relapse"?
Worsening of symptoms against the background of fever, stress, or heat exposure without a new lesion. Does not require changing DMT, only correcting the triggering factor.
See also: Stroke · Cranial nerves · Glucocorticoids · Immune cells · Neurology catalog · Clinical scales